The present invention relates to a method for sterilizating a dialyzer, especially a dialyzer for clinical use.
Recent progress in the art relating to artificial internal organs has been remarkable. Above all, various artificial kidneys have been created, miniaturized, improved in safety and made easy to use. Further, a dialyzer for use with the living body, based on the same principles, has been strenuously studied for use as an artificial liver or for utilization as an ultrafiltration apparatus for use with the living body.
In the field relating to sterilization of dialyzers for the living body, namely, artificial kidneys which have heretofore been used in actual practice, various methods have been used. These include the gaseous sterilization method, which uses ethylene oxide gas, and an alternative method which involves filling with an aqueous solution of formalin.
In the ethylene oxide gas method, a remarkable reduction of the performance of the dialyzer is sometimes encountered as a result of the sterilization procedure. Further, a very substantial preparation procedure is required, including washing for removal of poisonous residual gas, and of harmful substances produced by reaction with the sterilizing gas. Further, in the case of a hollow filament dialyzer which is one of the most advanced forms of dialyzer, it is necessary completely to replace the contents of the interiors of about 10,000 hollow filaments, each having an inner diameter of a few hundred microns, with physiological saline at the time of use. Indeed, if air or bubbles remain, circulation of blood may become obstructed, and this may become a cause of thrombosis. Further, the performance of a dialyzer is downgraded as a result of the sterilization procedure, and the valuable characteristics of the hollow filament dialyzer are at least partially lost. Further, the procedure of completely replacing the contents of the interiors of hollow filaments with physiological saline requires a remarkable amount of trouble and time.
The method of filling with an aqueous solution of formalin is said to have adequate sterilization effectiveness when a formalin solution of more than a certain concentration is used. However, the toxicity of the residual formalin at the time of use presents a safety problem. In order to completely wash and remove the formalin, washing for a very considerable time is necessary. Even then the problem remains regarding unfavorable side effects, which may be caused by even a trace of residual formalin. This process also presents another problem--that of disposal of the applied formalin solution.
On the other hand, sterilization by radial rays using gamma-rays or electron rays exerts a destructive influence on ordinary materials. Therefore, irradiation is limited to specific uses on materials having good resistance to the effects of radial rays. However, it is known that cellulose, polymethyl methacrylate and polyacrylonitrile, which are preferred for use as a semipermeable membranes and enhance the performance of an artificial kidney or a dialyzer for use with a living body, have poor resistance to the effects of such irradiation. Thus, they suffer great physical and chemical damage and their performance, extraction capability and strength are damaged.
Sterilization by application of radial rays can be practiced on a product that is completely wrapped and packaged. Accordingly, if the foregoing drawbacks were to be overcome, the use of radial rays would provide a very excellent sterilization method. The possibility of recontamination after sterilization would be eliminated and there would be no unfavorable side effects due to residual antibacterial agents.
One of the main reasons why sterilization by application of radial rays has not been effective in conjunction with most advanced hollow filament dialyzers resides in the toxicity of the extracts created by irradiation and in the destructive influence of radial rays, such as interference with the performance of the dialysis membranes. We have previously conducted studies of the problem of sterilization use of radial rays. We have found that such a dialyzer may be irradiated with radial rays while the dialyzer is filled or substantially filled with an aseptic inorganic aqueous solution which is harmless to a living body (such as aseptic water or physiological saline). Surprisingly, with such treatment it is possible to avoid significant destruction of the dialysis membranes. By so doing, it is possible to irradiate the dialyzer with an amount of radial rays which is sufficient to sterilize the dialyzer without producing undesirable extracts and without significant deterioration of the performance characteristics of the dialyzer.
It has further surprisingly been found, however, that it is necessary to reduce the number of contaminating bacteria to as small a value as possible before undertaking such a sterilization procedure. When the dialyzer is in a dry condition, or in a similar condition containing only a plasticizer such as glycerin for the semipermeable membrane, the dialyzer must be manufactured as aseptically as is possible. It is then possible to limit or prevent multiplication of bacteria to such a degree that they multiply to an almost negligible extent prior to commencement of the sterilization procedure. This serves to prevent the creation of pyrogens subsequent to the sterilization treatment.
When the dialyzer is completely or substantially completely filled with water or an ordinary aqueous solution bacteria usually multiply prior to sterilization treatment. It is nevertheless possible subsequently to sterilize the bacteria completely. However, if pyrogens are present in the residual killed bacteria, the patient is subject to the complications of chill and of fever after using such dialyzer.
An object of the present invention is to eliminate such disadvantages and to provide an excellent sterilization method for a dialyzer for use by a living person, with increased safety. Another object is to provide for reducing labor for preparing for dialysis.
Other objects of the present invention, including the simplicity and economy of the same and the ease with which it may be applied to existing dialysis equipment, will become apparent hereinafter.
In accordance with this invention, wherein the dialyzer has a semipermeable membrane, the dialyzer is subjected to the steps of:
(a) saturating the semipermeable membrane with a liquid containing an antibacterial agent; and
(b) irradiating the dialyzer with radiation rays sufficient to kill remaining microorganisms in the presence of the antibacterial agent.
In accordance with the present invention the dialyzer is washed after manufacture and is impregnated with aseptic water or physiological saline or a similar aqueous solution and an antibacterial agent. For example, the solution may be of a salt containing a proper amount of a substance having a bacteriostatic or antibacterial action, such as hydrogen peroxide. The solution is applied in an amount in excess of the amount needed for saturation of the semipermeable membrane. After impregnation with the water or solution, the dialyzer is wrapped or packaged in that condition and is thereafter (or even after further packing) irradiated with radiation rays in a predetermined amount to thereby sterilize the same.